PROJECT SUMMARY Type 1 Diabetes (T1D) affects nearly 3 million people in the United States over 20 million people globally. A subset of patients have unstable T1D because they possess poor glycemic control and severe hypoglycemia unawareness. While whole organ pancreas and islet transplantation can cure unstable T1D, these treatments are limited by immunosuppression therapy and scarcity of donor tissue. In contrast, encapsulating islets within an immunoprotecting membrane is a promising approach to eliminate the need for immunosuppression, but previous attempts suffered from low mass transfer rates of oxygen, glucose, and insulin in diffusion-based devices. In order to solve the limitations of diffusion, previous groups tested intravascular convection-based devices and showed some promise, but they provided insufficient ultrafiltration rates to provide sufficient islet oxygenation and glucose-insulin kinetics. In contrast, Silicon Kidney is commercializing the silicon nanopore membrane (SNM), which produces high levels of ultrafiltrate (>10x polymer membranes used in previous ultrafiltrate-based BAP devices) at physiologic blood pressures, providing exceptional convective mass transfer enabling a functional BAP. To further enhance islet oxygenation, perfluorocarbons, which are high oxygen capacity materials, can be incorporated into the islet cell scaffold to mimic the oxygen storage and release properties of hemoglobin by allowing oxygen to be stored during the islet?s low oxygen consumption state (fasting state) and released during the islet?s high oxygen consumption state (post-meal). In this Phase I SBIR project, we will combine the SNM-enabled convection and a perfluorocarbon-based cell scaffold to demonstrate unprecedented islet oxygenation and function, while allowing a reduction in overall device size.